The term ‘garbha’ literally means fetus or embryo. In current medical terms, embryo is the early stage of development of a multicellular organism that begins just after fertilization. It continues through the formation of body structures, such as tissues and organs.[1] A fetus is unborn offspring that develops from embryo.[2]This article deals with description of embryogenesis, factors influencing its development in womb and prenatal life.
| Section/Chapter/topic | Sharira / Garbha |
|---|---|
| Authors | Anagha S., Deole Y.S. |
| Reviewed by | Basisht G. |
| Affiliations | Charak Samhita Research, Training and Development Centre, I.P.G.T.& R.A., Jamnagar |
| Correspondence email | carakasamhita@gmail.com |
| Publisher | Charak Samhita Research, Training and Development Centre, I.T.R.A., Jamnagar, India |
| Date of first publication: | January 11, 2021 |
| DOI | 10.47468/CSNE.2021.e01.s09.040 |
Etymology and derivation
The word ‘garbha’ is derived from Sanskrit root “gru” by adding the suffix “bhan”.It means a fetus or embryo, a child, the belly, a hole, and hollow.[3]
It is synonymous to womb. Its root is also traced in ‘grabha’, which means to conceive, having in the interior, containing, filled with, inner apartment, sleeping room, interior chamber, adytum, sanctuary of a temple, and the inside, middle, or interior of anything.[4]
Definition
Garbha (embryo) is formed by union of sperm (shukra), ovum (shonita) and soul/conscious (jeeva or atma) in the womb (kukshi).[SAT-B.376][5] [Cha. Sa. Sharira Sthana 4/5]
Apart from the mere combination of sperm and ovum, the role of soul and the influence of subtle elements of evolution (prakriti and vikara) are important in development of embryo. [Su. Sa. Sharira Sthana 5/3]
The development in prenatal life can be divided into two phases:
1. Embryonic development: The first eight weeks (weeks 1 - 8) after fertilization is the embryonic period. It is also considered the organogenic period, when most organs within the embryo have begun to form.[6]
2. Fetal development: The prenatal period of 9 weeks to 37 weeks is fetal period. It is a time of extensive growth in size and mass as well as ongoing differentiation of organ systems. Clinically this period is generally described as the second trimester and third trimester.[7]
Essential factors for conception (garbha sambhava samagri)
Following four factors are essential for the conception and the health of an embryo:
1. Fertile period(ritu) or healthy environment
2. Uterus/female reproductive organs(kshetra) or healthy womb
3. Nourishment(ambu) or healthy nourishing body constituents inside womb
4. Seeds (sperm and ovum) (beeja) or healthy genes. [Su. Sa. Sharira Sthana 2/33]
These four factors determine and influence health of progeny. These four factors are essential for natural pregnancy. In case of female infertility, following methods are developed.
Contemporary methods of conception
With the advances in medical field, scientists have developed various techniques for artificial conception without sexual intercourse. It includes methods of artificial insemination like Intrauterine insemination (IUI) and fallopian tube sperm perfusion.[8]
Furthermore, assisted reproductive technology is developed. This involves all the procedures like manipulation of gametes and embryos outside the body for treatment of infertility.
In vitro fertilization and embryo transfer (IVF-ET): Approximately 50,000 to 100,000 capacitated sperms are placed into the culture media containing the oocyte within 4-6 hours of retrieval. The fertilized ova at the 6-8 blastomere stage are placed into the uterine cavity close to the fundus about 3 days after fertilization through a fine flexible soft catheter transcervically.[9]
Gamete intra fallopian transfer (GIFT): Two collected oocytes along with approximately 200,000-500,000 motile sperm for each fallopian tube are taken and injected to the distal end of the fallopian tube through laparoscope.[9]
Zygote intra fallopian transfer (ZIFT): The placement of the zygote following one day of in vitro fertilization into the fallopian tube.[9]
Intra Cytoplasmic Sperm Injection (ICSI): A single spermatozoa or even spermatid is injected directly into the cytoplasm of an oocyte by micro puncture of the zona pellucida.[9]
Gestational Carrier Surrogacy: In this procedure, a fertilized egg is placed into the uterus of a surrogate (gestational carrier) if the mother is not having a functional uterus. [10]
Embryogenesis and fetal development(garbhavakranti)
When a healthy sperm and a healthy ovum get conceived in a healthy womb at a proper time, the soul (atma) with mind (sattva) form the embryo (garbha). This grows further with suitable nourishment by the wholesome nutrient fluid (rasa) and proper regimen (garbhini paricharya). Thereafter the fetus is formed with all sensory and motor organs (indriya) and all body parts. This is endowed with excellence of strength (bala), complexion (varna), psyche (sattva) and compact structure (samhanana) for delivery in proper time. [Cha. Sa. Sharira Sthana 3/3]
Role of panchamahabhuta in embryogenesis
The embryo is constituted of five great elements (mahabhuta) and consciousness (chetana). Hence, the holistic human being (purusha) is also known as ‘six elemental’ (shad dhatvatmaka purusha). [Cha. Sa. Sharira Sthana 4/6] The Purusha (microcosm) is developed from loka(macrocosm). The five fundamental elements are sources for various functions of holistic human being. All the five elements (mahabhuta) play respective roles during embryogenesis and foetal development. [Su. Sa. Sharira Sthana 5/3] Research on this concept may provide more insights in treatment of disorders of respective body components. For example, the sound vibrations can have effect on functions of akasha mahabhuta. This can be helpful in promotion of good prenatal health. Some researches on effect of music therapy on fetal development are in progress. A complete program for prenatal health and wellness called ‘garbha samskara’ is regularly advised and conducted in various institutions of India.[11]
Table 1: Functions and body components developed from panchamahabhuta*
| Mahabhuta | Functions | Body components |
|---|---|---|
| Akasha | Multidimensional development (vivardhana), spaces occupied by subtle energy potentials | sound (shabda),auditory system (shabdendriya),lightness (laghava),minuteness (saukshmya),division (viveka),channels (srotas),all orifices (sarvachidra samuha),oral cavity (mukha),throat (kantha),abdominal cavity (koshta) |
| Vayu | Cell division, Generation and control of movements, impulses | sense of touch (sparsha),organ of sense of touch (sparshanendriya),activity of body (chehsta/parispandana),lightness (laghava),activities of body (sarva sharira spandana),formation or transformation of dhatus (dhatu-vyuhana),expiration (ucchvasa),dryness (raukshya),impulsion (prerana) |
| Agni | Transformation | form (rupa),ophthalmic apparatus (chakshu-indriya),metabolism (pakti),body heat (ushma),complexion (varna),splendour (bhrajishnuta),intolerance (amarsha),sharpness (taikshnya),valour (shaurya),feeling of heat (santapa),light (prakasha),metabolic enzymes (pitta),sharpness/brightness (teja),intellect (medha),growth of body (sharira vridhi) |
| Jala | Moisture, Nourishment for the growth of the tissue. | taste (rasa),gustatory system (rasanendriya),coldness (shaitya),softness (mardava),unctuousness (sneha),semen (shukra),urine (mutra),plasma (rasa dhatu),moisture (kleda),blood (rakta),fat (vasa /medas),sweat (sweda),flesh (mamsa) |
| Prithvi | Compact structure and integrity (samhanana) of cells | smell(gandha),olfactory organs(ghranendriya),heaviness(gaurava),stability(sthairya),stiffness or structure of body(murti),hairs(kesha),bones(asthi),patience(dhairya),nails (nakha) |
*[Cha.Sa. Sharira Sthana 4/12], [ A.S. Sharira Sthana 5/9-13], [A.Hr.Sharira Sthana 3/3-4], [K.Sa.Sharira Sthana 3 / 4]
Role of shad bhava (six sources of origin) of garbha
The embryo develops from six major sources:
1. Maternal factors (matruja)
2. Paternal factors (pitruja)
3. Spiritual elements (atmaja)
4. Psychological elements (satvaja)
5. Adaptability (satmyaja)
6. Nutritional components (rasaja)
Table 2: Body parts/ components derived from six sources (shad bhava)*
| Maternal(matruja) | Paternal(pitruja) | Soul/spiritual (atmaja) | Mind/psychological(satwaja) | Adaptations(satmyaja) | Nutritional(rasaja) |
|---|---|---|---|---|---|
| muscle (mamsa) | hair (kesha) | sense organs (indriya) | likings (bhakti) | power(virya) | growth of body (sharira upachaya) |
| blood (rakta) | beard and moustache (shmashru) | knowledge (jnana) | conduct (sheela) | freedom from diseases (arogya) | energy or strength(bala) |
| fat (meda) | body-hair (loma) | critical analysis (vijnana) | purity (shaucha) | strength or energy (bala) | complexion (varna) |
| bone marrow (majja) | bones(asthi) | longevity (ayu) | hatred (dwesha) | normal complexion (varna) | health (sthiti) |
| heart (hrudaya) | nails (nakha) | happiness and sorrow (sukha -dukha) | memory (smriti) | intellect (medha) | unhealthy state (hani) |
| umbilicus (nabhi) | teeth (danta) | birth in specific species (nana yoni utpatti) | attachment (moha) | progress (utthana) | manifestation of different body parts (sharira abhinivrutti) |
| liver (yakrut) | veins (sira) | Self-realization (atmajnana) | detachment (tyaga) | absence of idleness(analasya) | attachment of life or strength with body (prananubandha) |
| spleen (pliha) | tendons (snayu) | psyche (manas) | strong desire not to part with (matsarya) | satisfaction (samtosha) | contentment (trupti) |
| intestine (antra) | arteries (dhamani) | appearance (akruti vishesha) | valour (shaurya) | absence of greed(alolupatwa) | nourishment (pushti) |
| anus (guda) | semen (retas) | voice (svara vishesha) | fear (bhaya) | normal voice(svarasampata) | enthusiasm (utsaha) |
| skin (twak) | -- | specific complexion (varna vishesha) | anger (krodha) | normal seed (bijasampata) | maintenance of body (vrutti) |
| kidney (vrikka) | -- | longing &hatred(Iccha-dwesha) | drowsiness(tandra) | constant happiness(praharshadhikya) | absence of greed (alaulyam) |
| urinary bladder (basti) | -- | consciousness (chetana) | enthusiasm (utsaha) | perspicuity of sense organs (indriya prasada) | -- |
| rectum (purishadhana) | -- | intellect (buddhi) | sharpness (taikshnya) | high quality of ojas | -- |
| stomach (amashaya) | -- | power of retention (dhriti) | softness (mardava) | life span (ayu) | -- |
| small intestine (pakwashaya) | -- | memory (smriti) | seriousness (gambhirya) | -- | -- |
| large intestine (sthulantra) | -- | egoism (ahankara) | -- | -- | |
| upper part of rectum (uttaraguda) | -- | endeavour (prayatna) | -- | -- | -- |
| lower part of rectum (adharaguda) | -- | Transmigration (sthanantara gamana) | -- | -- | -- |
- [Cha. Sa. Sharira Sthana 3/6-13], [Su Sa Sharira Sthana 3/33]
[A. S. Sharira Sthana 5/1519], [A. Hr Sharira Sthana 3/7]
All the physical components of foetus are derived from maternal and paternal factors. Most of the paternal organs seem to be ectodermal, and maternal organs to be endodermal and mesodermal in origin. The other factors like adaptability (satmyaja), nourishment (rasaja) and psychological (sattvaja) are influenced by diet and lifestyle regimen of mother. The food taken by the mother provides proper nutrition to herself and foetus in the womb. The quality and quantity of diet of mother have great impact on the growth and development of the foetus. The psychological status of mother and environmental factors also influences the foetal development. The epigenetic and genetic research on these connections may be useful for better understanding of health and origin of disease.
Factors influencing embryonic development
As per contemporary views, embryonic development is the result of interactions between the genetic program in the chromosomes of each zygote and the female genital tract.[12]
The factors influencing embryonic development can be broadly divided into three.
a) Autocrine factors: mostly growth factors, generated by the embryo for sustaining its own development.
b) Paracrine factors: growth factors and specific proteins, generated by the oviduct which reach the conceptus.
c) Environmental factors: various substances like energy substrates, ions, amino acids, vitamins - which generate the “perfect” medium for an embryo to grow.
The successful embryonic development requires the balanced combination of all these factors. Genetic, nutritional, environmental, uteroplacental, and fetal factors have been suggested to influence fetal growth. Uteroplacental and umbilical blood flow and transplacental glucose and fetal insulin are major determinants of fetal growth.[13]
Month wise development of embryo and foetus
The development of embryo and foetus in gestational life is described in all major Ayurveda texts. The method of assessment was mainly based on clinical observations. In contemporary practices, the development of embryo can be assessed by highly advanced technologies like ultrasonography. The weekly development is observed and noted. The following table depicts both views.
Table 3: Embryonic and fetal development
| Month | Description in Ayurveda texts* | Description in contemporary medical texts[6][7] |
|---|---|---|
| 1st month | Attains the consistency resembling shleshma(mucoid character),or jelly mass(kalala) in which all the body parts though present are not conspicuous.
1st day-jelly mass(kalala) 10th day-buble like(budbuda) 15th day-solid (ghana) 20th day-muscle like (mamsa panda) 25th day-more conspicuous |
Week 1- fertilized oocyte, zygote, pronuclei, morula cell division with reduction in cytoplasmic volume, blastocyst formation of inner and outer cell mass, loss of zona pellucida, free blastocyst, attachment of blastocyst
Week 2- implantation, extraembryonic mesoderm, primitive streak, gastrulation Week 3 - gastrulation, notochordal process, primitive pit, notochordal canal, Somitogenesis, cardiac primordium, head fold Week 4 - neural fold fuses, rostral neuropore closes, caudal neuropore closes |
| 2nd month | Converted into Compact or solid form
•Knot like structure (pinda/ghana) -male (purusha), •elongated, muscle like structure(peshi)- female(stree), •elevated/irregular shape (arbuda)- eunuch (napumsaka) 50th day- formation of buds of future body parts (ankura) |
Week 5- leg buds, lens placode, pharyngeal arches, lens pit, optic cup, lens vesicle, nasal pit, hand plate
Week 6-nasal pits moved ventrally, auricular hillocks, foot plate, finger rays Week 7- ossification commences, straightening of trunk Week 8- upper limbs longer and bent at elbow, hands and feet turned inward, eyelids, external ears, rounded head, body and limbs |
| 3rd month | •All sense organs (sarvendriya) and all other organs (sarva angavayava) are manifested simultaneously.
•five buds or projections (panchapindika)- arms (hasta),legs (pada) and head(shira),differentiation of major and minor parts (anga-pratyanga) •achieves consciousness and feelings(vedana) |
9-12 weeks – In the beginning of 9th week, head constitutes half of the crown-heel length of the foetus, and by the end of 12th week, crown-rump length almost doubles.
Broad face, eyes get widely separated, ears-low set, eye lids get fused, by the end of 12th week-primary ossification centres appear in the cranium and long bones, external genitalia develop, intestinal coils are clearly visible |
| 4th month | •Garbha gets stabilized (sthiratwa)
•All major and minor parts become clearly demarcated, expresses desires in objects of sense organs. Head gets excellent development (shira saravat bhavet) during 3 ½ months and appearance of lanugo(loma) |
13-16 weeks-Growth - rapid growth continues
•Head - head has straightened up •eyes at the front part of the face but still widely separated •outer ear has moved (relatively) from upper part of neck to the side of the head •Musculoskeletal - ossification is proceeding •skeleton now visible on an x-ray •Integumentary - body is covered with lanugo |
| 5th month | •Excessive increase of muscle tissue (mamsa) and blood (rakta)
•Mind (manas) becomes more enlightened •foetus becomes more capable of living (sujeeva) |
17-20 weeks-Growth - Length growth begins to slow.
•Body parts have acquired their relative proportions. •Integumentary - vernix caseosa •Sebaceous glands begin to secrete and vernix caseosa comes to cover the skin to prevent damage by amniotic fluid. •Neural - Spinal cord myelinization begins •Adipose Tissue - brown fat is forming •Musculoskeletal - active movements of the fetus in the uterus (kicks) |
| 6th month | Rapid increase in bala(strength) and varna(complexion),More enlightening of buddhi(intellect),Manifestation of kesha(hairs on head), loma(body hairs), nakha(nails), asthi(bones), snayu(tendons), twak(skin),increase in strength(bala), complexion(varna) and vital power in foetus(ojas),quivering (prasphurana) | 21-25 weeks- Integumentary / Vision - eyelids and eyebrows developed
•Lanugo a darker color and vernix caseosa is thicker. •skin is sometimes very wrinkled (high growth, lack of subcutaneous fat) •fingernails are visible •Growth - face and body are usually as they will be at birth. •Fetuses born after the 25th week of gestation are generally viable |
| 7th month | Differentiation of all the major and minor parts becomes evident,Completeness of all the body parts in terms of growth and development,optimum level of vata-pitta-kapha | 26-29 week-integumentary / Vision - eyes are opened again and eyebrows and eyelashes are well formed
•Pupillary membrane disappears. •Integumentary - hair grows, subcutaneous adipose tissue deposits round the whole body, becomes chubby and plump |
| 8th month | Unstable movement of vitality (ojas) from foetus to mother and vice versa through the channels of circulation of nutrient fluid.
Digestive enzymes (pachakagni) starts functioning. |
30-34 weeks-Integumentary - body becomes chubby and the skin is pink
•fingernails have reached the ends of the fingers •toe nails are visible Genital - testicles descend |
| 9th month | Cheshta (activities) are more apparent | -- |
- [Cha. Sa. Sharira Sthana 4/9-24], [Su. Sa. Sharira Sthana 3/18-30],
[A. S. Sharira Sthana 2/13-28],[A. Hr. Sharira Sthana 1/37-63] [Ka. Sa. Sharira Sthana 2/4-10], [B.P. Pur 3/289-307],[Ha. Sa. Shashtha Sthana 1/17-22]
Disorders during embryonic life and their diagnosis
The abnormalities occurring in the embryonic development can be attributed to the following:
a) Genetic factors
b) Environmental factors
c)Idiopathic(unknown) factors.[14]
The genetic factors are related to maternal and paternal age, family history, ethnic background etc.[15]
Environmental factors includes maternal infections (Eg-TORCH infection), maternal diet (eg- folic acid deficiency leading to neural tube defects), life style (adverse effects of smoking, alcoholism etc.) and certain drugs or chemicals(teratogenic effect).The environmental factors that cause or lead to any of the abnormalities are described as teratogens.[16]
Prenatal diagnosis are the clinical tools used to determine both normal and abnormal development.Many diagnostic techniques are being applied to diagnose human embryonic development.
The two major classes of techniques are invasive and non-invasive testing.[17]
A Combined first trimester screening test (cFTS) involves a maternal ultrasound scan and blood tests at 11-13weeks of pregnancy. Genetic screening includes maternal serum alpha-fetoprotein (MSAFP), triple test at 15-18 weeks for mother at risk of carrying a fetus with neural tube defects, down syndrome or another chromosomal anomaly.
Non-Invasive Prenatal Testing (NIPT) include new techniques that analyzes cell-free fetal DNA circulating in maternal blood or from fetal cells in the cervical canal.
Invasive procedures include amniocentesis, chorionic villi sampling, fetal blood sampling etc.
Ayurveda texts describe the diseases in prenatal life under the category of congenital disorders (sahaja and garbhaja vyadhi).[A.S.Sutra Sthana 22/1] It also describes specific diseases occurring in progeny due to vitiation of channels carrying shukra and abnormalities of shukra dhatu. [Cha. Sa. Sutra Sthana 28/18-19].The disorders due to improper diet and lifestyle of mother are described under garbhaja vyadhi (jananyapacharat) [A. S. Sutra Sthana 22/1]
Current researches
- During early embryogenesis, the pro-embryo consists of two domains, the embryo proper and the suspensor. Recent studies have revealed that the suspensor plays an important role in early embryogenesis and the process of suspensor formation and degeneration may provide a unique model for studies on cell division pattern, cell fate determination, and cell death.[18] The different shapes attributed to the early embryonic development like jelly mass, knot like structure, elongated muscle like structure, irregular elevation etc. described in Ayurveda embryology may be explored on the basis of these findings.
- Precise gene expression ensures proper stem and progenitor cell differentiation, lineage commitment and organogenesis during mammalian development. ATP-dependent chromatin-remodeling complexes utilize the energy from ATP hydrolysis to reorganize chromatin and, hence, regulate gene expression. These complexes contain diverse subunits that together provide a multitude of functions, from early embryogenesis through cell differentiation and development into various adult tissues.[19] These cell differentiation processes are mainly attributed to the action of vata dosha.
- The maternal-to-embryonic transition consists of critical developmental processes including maternal RNA depletion and embryonic genome activation. In recent years, key maternal proteins encoded by maternal-effect genes have been determined, primarily using genetically modified mouse models. These proteins are implicated in various aspects of early embryonic development including maternal mRNA degradation, epigenetic reprogramming, signal transduction, protein translation and initiation of embryonic genome activation.[20]These shows the importance and main contribution of maternal factor (matruja bhava) in the early stage of embryonic development. Diseases that occur due to mutation in the mitochondrial genome are inherited only from the mother, as only the ovum contains mitochondrial genetic material.[21]
- Advanced paternal age is well-documented to be associated with new dominant mutations and paternal exposures to drugs may increase the risk of adverse fetal outcome.[22], [23]
- Epigenetic mechanisms are influenced by several factors like development in utero and in childhood, environmental chemicals, drugs and pharmaceuticals, aging, and diet. Example- Methyl groups, an epigenetic factor found in some dietary sources, can tag DNA and activate or repress genes which is known as DNA methylation. So, the six procreative factors (Shad garbhakara bhava) have an important role as causative factors of congenital, hereditary, and genetic anomalies by mutation and epigenetics.[24]
- Designer babies are babies from embryos formed by in-vitro fertilization (IVF). They are either created from an embryo selected by preimplantation genetic diagnosis (PGD) or genetically modified in order to influence the traits of the resulting children. The primary aim of creating designer babies is to avoid heritable diseases coded by mutations in DNA.[25]
More information
References:
- ↑ Available from https://en.wikipedia.org/wiki/Embryo#:~:text=An%20embryo%20is%20the%20early,such%20as%20tissues%20and%20organs. Cited on 08/01/2021
- ↑ Available from https://en.wikipedia.org/wiki/Fetus Cited on 08/01/2021
- ↑ Jha Srujan. Amarkosha online application.
- ↑ Available from https://www.wisdomlib.org/definition/garbha cited on 21/12/2020
- ↑ Available from http://namstp.ayush.gov.in/#/sat
- ↑ 6.0 6.1 https://embryology.med.unsw.edu.au/embryology/index.php/Embryonic_Development
- ↑ 7.0 7.1 https://embryology.med.unsw.edu.au/embryology/index.php/Fetal_Development
- ↑ D.C Dutta,D.C Dutta’s text book of Gynaecology, edited by HiralalKonar,Infertility, Jaypee brothers medical publishers, New delhi, edition 7, 2016, chapter 17, page no:203
- ↑ 9.0 9.1 9.2 9.3 D.C Dutta,D.C Dutta’s text book of Gynaecology, edited by HiralalKonar,Infertility, Jaypee brothers medical publishers, New delhi, edition 7, 2016, chapter 17, page no:206
- ↑ D.C Dutta,D.C Dutta’s text book of Gynaecology, edited by HiralalKonar,Infertility, Jaypee brothers medical publishers, New delhi, edition 7, 2016, chapter 17, page no:207
- ↑ Available from http://www.nia.nic.in/pdf/Program_Garbhasanskar_Antenatal_Program_2020_Batch_V_VI.pdf cited on 08/01/2021
- ↑ Fulvio Gandolfi,Autocrine, paracrine and environmental factors influencing embryonic development from zygote to blastocyst,Theriogenology,Volume 41, Issue 1,1994,Pages 95-100,ISSN 0093-691X, https://doi.org/10.1016/S0093-691X(05)80053-6.
- ↑ Vorherr H. Factors influencing fetal growth. Am J Obstet Gynecol. 1982 Mar 1;142(5):577-88. doi: 10.1016/0002-9378(82)90765-7. PMID: 7036747.
- ↑ https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development.
- ↑ https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Genetic
- ↑ https://embryology.med.unsw.edu.au/embryology/index.php/Human_Abnormal_Development#Environmental
- ↑ https://embryology.med.unsw.edu.au/embryology/index.php/Prenatal_Diagnosis
- ↑ Peng X, Sun MX. The suspensor as a model system to study the mechanism of cell fate specification during early embryogenesis. Plant Reprod. 2018;31(1):59‐65. doi:10.1007/s00497-018-0326-5
- ↑ Hota SK, Bruneau BG. ATP-dependent chromatin remodeling during mammalian development. Development. 2016;143(16):2882‐2897. doi:10.1242/dev.128892.
- ↑ Zhang K, Smith GW. Maternal control of early embryogenesis in mammals. Reprod Fertil Dev. 2015;27(6):880‐896. doi:10.1071/RD14441
- ↑ Dhiman K, Kumar A, Dhiman KS. Shad Garbhakara Bhavas vis-a-vis congenital and genetic disorders. Ayu. 2010;31(2):175-184. doi:10.4103/0974-8520.72384
- ↑ Robaire B, Hales BF. The male germ cell as a target for drug and toxicantaction. In: Gagnon C, ed. The Male Gamete: From Basic Science to Clinical Applications. Boca Raton, Fla: Cache River Press; 1999:469-74
- ↑ Savitz. Paternal Exposure to Drugs Reviewand Environmental Chemicals: Effects onProgeny Outcome Journal of Andrology, Vol. 22, No. 6,page no- 930 November/December 2001- American Society of Andrology
- ↑ Dhiman K, Kumar A, Dhiman KS. Shad Garbhakara Bhavas vis-a-vis congenital and genetic disorders. Ayu. 2010;31(2):175-184. doi:10.4103/0974-8520.72384
- ↑ Ronald T.K. Pang, P.C. Ho,Designer babies,Obstetrics, Gynaecology & Reproductive Medicine,Volume 26, Issue 2,2016,Pages 59-60,ISSN 1751-7214,https://doi.org/10.1016/j.ogrm.2015.11.011